(04-09-08) Marine Omega-3 PUFAs Reduce NSAID Use in Patients with Rheumatoid Arthritis

Rheumatoid arthritis is a highly inflammatory, chronic autoimmune disease of the joints, characterized by painful swollen joints. It can progress to joint destruction, deformity and disability. The condition afflicts women 2 to 3 times more frequently than men, usually after age 55. There is no cure and treatment focuses on managing pain and retarding disease progression. Recent concern about the side effects associated with non-steroidal anti-inflammatory drugs (NSAIDs), widely used to ease pain, has shifted attention to less harmful agents, particularly long-chain omega-3 fatty acids (n-3 LC-PUFAs).
Because of their anti-inflammatory effects, n-3 LC-PUFAs in gram quantities have been used successfully to treat patients with rheumatoid arthritis. Although some trials have observed no clinical benefits with n-3 LC-PUFAs given at <2 g/day, it is important to furnish a sufficient dose, usually 3 g/day or more. In addition to improving the patient?s clinical condition, consumption of fish oils may permit a reduction in the amount of NSAIDs needed to control pain or end their use.
Additional benefits of adjunct therapy with n-3 LC-PUFAs or fish oil in
rheumatoid arthritis patients should be a lower risk of cardiovascular disease and minimal, if any, gastrointestinal side effects.

The investigators in this study recruited 97 patients over the age of 18 (69 females, 28 males) from two locations in Scotland, UK, who had stable rheumatoid arthritis and were not taking n-3 LC-PUFAs, or other fatty acid supplements or prednisolone in excess of 7.5 mg/day. All patients were taking NSAIDs and at least 75% were also consuming other disease-modifying anti-rheumatic drugs, such as methotrexate or sulphasalazine.

Patients were randomized to consume 10 capsules/day of a blend of cod liver and fish oil providing a total of 1.5 g eicosapentaenoic acid (EPA) and 700 mg docosahexaenoic acid (DHA) or air-filled placebo capsules for 9 months.
Treatment supplements also contained vitamins A, D and E at levels equal to or below the US Dietary Reference Intakes. Patients were clinically assessed at baseline, 4, 12, 24 and 36 weeks. Patients recorded their daily doses of NSAIDs throughout the study and were encouraged to reduce their dose from the 12th week forward. The primary outcome measure was reduction of NSAID use by >30%.
Fifty-eight participants (60%) completed the 9-month study.

At the end of 9 months, significantly more patients consuming the n-3 LC-PUFAs (19 of 49 or 39%) compared with those on the placebo (5 of 48 or 10%) reduced their daily NSAID requirement by more than 30% (Figure). On average, the reduction in NSAIDs was greater in the treated patients (26%) compared with the controls (9%). When results of only those patients who completed the study were analyzed, 19 of 32 (59%) treated patients reduced their need for NSAIDs by >30% compared with 5 of 26 control patients (19%). The difference between groups was statistically significant, P=0.002, in intention-to-treat analysis.
Those consuming n-3 LC-PUFAs reduced their NSAID requirement by an average of 40%, while those taking the placebo reduced their NSAID use by 16%. Results were similar, but slightly strengthened, when the analysis was restricted to patients who did not increase their dose of other medications.

Clinical assessments revealed that the reduction in NSAID use was achieved without a worsening of disease activity or a significant increase in the use of other disease-modifying drugs. In fact, there was a small, but significant, improvement in the mean changes from baseline in the visual analog scores for pain at 9 months in patients taking the n-3 LC-PUFAs (-6.7 ? 3.1 SEM mm) compared with the placebo patients (1.9 ? 2.4 SEM mm). Other clinical assessments of both groups did not improve over the course of the study.
Reported side effects were mild?nausea, vomiting, diarrhea, flatulence,
inability to swallow the capsules?and did not differ between the groups.
Reasons for patient withdrawal from the study did not differ between the groups and included adverse events related and unrelated to the study medication, voluntary withdrawal and lack of efficacy of the study medication.

These findings confirm the efficacy of n-3 LC-PUFAs at >2 g/day as an adjunct treatment for patients with rheumatoid arthritis. The study showed a significant decrease in the use of NSAIDs?39% of patients who started the study reduced their need for NSAIDs by more than a third and almost two-thirds of patients who completed the study achieved this reduction. With a substantial number of serious adverse effects associated with taking NSAIDs, these findings buttress previous reports that, for many patients, dependence on this class of drugs can be substantially reduced or avoided by taking n-3 LC-PUFAs or fish/cod liver oils. This study also confirms the need to allow sufficient time
for improvements to accrue. Significant reduction in NSAID use was observed at 24 weeks, but not at 12 weeks. Others have reported that the maximum effect of fish oil on the reduction in NSAID medication was not observed until 12 months.
Patients complained about the large number (10/day) and size of the capsules, but other investigators have circumvented this problem by using liquid fish oil or more concentrated supplements. It should be noted that the treatment alsoincluded fat-soluble vitamins that were not provided to the control group.
Thus, these results may have been influenced by these nutrients as well. As the evidence accumulates, clinicians can consider fish oil as a front line treatment for patients with rheumatoid arthritis that improves their symptoms, reduces NSAID use and provides collateral health benefits.

Galarraga B, Ho M, Youssef HM, Hill A, McMahon H, Hall C, Ogston S, Nuki G, Belch JJ. Cod liver oil (n-3 fatty acids) as a non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatol (Oxford) 2008;47:665-669.

Source: PubMed

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